HCSGD entry for FOXO3
1. General information
| Official gene symbol | FOXO3 |
|---|---|
| Entrez ID | 2309 |
| Gene full name | forkhead box O3 |
| Other gene symbols | AF6q21 FKHRL1 FKHRL1P2 FOXO2 FOXO3A |
| Links to Entrez Gene | Links to Entrez Gene |
2. Neighbors in the network
This gene isn't in PPI subnetwork.
3. Gene ontology annotation
GO ID | GO term | Evidence | Category |
|---|---|---|---|
| GO:0000122 | Negative regulation of transcription from RNA polymerase II promoter | IMP | biological_process |
| GO:0001542 | Ovulation from ovarian follicle | IEA | biological_process |
| GO:0001544 | Initiation of primordial ovarian follicle growth | IEA | biological_process |
| GO:0001547 | Antral ovarian follicle growth | IEA | biological_process |
| GO:0001556 | Oocyte maturation | IEA | biological_process |
| GO:0003677 | DNA binding | IDA | molecular_function |
| GO:0003700 | Sequence-specific DNA binding transcription factor activity | IDA IEA | molecular_function |
| GO:0005515 | Protein binding | IPI | molecular_function |
| GO:0005634 | Nucleus | IDA IEA | cellular_component |
| GO:0005654 | Nucleoplasm | TAS | cellular_component |
| GO:0005737 | Cytoplasm | IDA | cellular_component |
| GO:0005829 | Cytosol | IBA IEA | cellular_component |
| GO:0006351 | Transcription, DNA-templated | IEA | biological_process |
| GO:0006417 | Regulation of translation | IDA | biological_process |
| GO:0006974 | Cellular response to DNA damage stimulus | IBA | biological_process |
| GO:0007173 | Epidermal growth factor receptor signaling pathway | TAS | biological_process |
| GO:0007389 | Pattern specification process | IBA | biological_process |
| GO:0008286 | Insulin receptor signaling pathway | IBA | biological_process |
| GO:0008301 | DNA binding, bending | IBA | molecular_function |
| GO:0008543 | Fibroblast growth factor receptor signaling pathway | TAS | biological_process |
| GO:0009790 | Embryo development | IBA | biological_process |
| GO:0009888 | Tissue development | IBA | biological_process |
| GO:0016020 | Membrane | IEA | cellular_component |
| GO:0019901 | Protein kinase binding | IPI | molecular_function |
| GO:0030330 | DNA damage response, signal transduction by p53 class mediator | IEA | biological_process |
| GO:0038095 | Fc-epsilon receptor signaling pathway | TAS | biological_process |
| GO:0042127 | Regulation of cell proliferation | IBA | biological_process |
| GO:0042593 | Glucose homeostasis | IEA | biological_process |
| GO:0043525 | Positive regulation of neuron apoptotic process | IMP | biological_process |
| GO:0043565 | Sequence-specific DNA binding | IDA IEA | molecular_function |
| GO:0045087 | Innate immune response | TAS | biological_process |
| GO:0045648 | Positive regulation of erythrocyte differentiation | IDA | biological_process |
| GO:0045893 | Positive regulation of transcription, DNA-templated | IDA IEA | biological_process |
| GO:0045944 | Positive regulation of transcription from RNA polymerase II promoter | IDA | biological_process |
| GO:0048011 | Neurotrophin TRK receptor signaling pathway | TAS | biological_process |
| GO:0048015 | Phosphatidylinositol-mediated signaling | TAS | biological_process |
| GO:0097192 | Extrinsic apoptotic signaling pathway in absence of ligand | IEA | biological_process |
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4. Expression levels in datasets
- Meta-analysis result
| p-value up | p-value down | FDR up | FDR down |
|---|---|---|---|
| 0.1360760381 | 0.7342916113 | 0.7444532835 | 1.0000000000 |
- Individual experiment result
( "-" represent NA in the specific microarray platform )
( "-" represent NA in the specific microarray platform )
| Data source | Up or down | Log fold change |
|---|---|---|
| GSE11954 | Down | -0.1051106269 |
| GSE13712_SHEAR | Down | -0.1684455237 |
| GSE13712_STATIC | Down | -0.0456043600 |
| GSE19018 | Up | 0.4364831291 |
| GSE19899_A1 | Down | -0.1484576757 |
| GSE19899_A2 | Up | 0.1622028528 |
| PubMed_21979375_A1 | Up | 0.7088381256 |
| PubMed_21979375_A2 | Up | 0.8487072072 |
| GSE35957 | Up | 0.1762374016 |
| GSE36640 | Down | -0.2303891486 |
| GSE54402 | Up | 0.0804310055 |
| GSE9593 | Up | 0.2882921823 |
| GSE43922 | Down | -0.0504848461 |
| GSE24585 | Up | 0.0599749797 |
| GSE37065 | Down | -0.1288001702 |
| GSE28863_A1 | Up | 0.5902560511 |
| GSE28863_A2 | Up | 0.4456782125 |
| GSE28863_A3 | Down | -0.1310048397 |
| GSE28863_A4 | Down | -0.1794586349 |
| GSE48662 | Up | 0.0742162065 |
5. Regulation relationships with compounds/drugs/microRNAs
- Compounds
Not regulated by compounds
- Drugs
Not regulated by drugs
- MicroRNAs
- mirTarBase
- mirTarBase
MiRNA_name | mirBase ID | miRTarBase ID | Experiment | Support type | References (Pubmed ID) |
|---|---|---|---|---|---|
| hsa-miR-222-3p | MIMAT0000279 | MIRT000433 | qRT-PCR//ChIP//Luciferase reporter assay//Western blot//Northern blot | Functional MTI | 20388878 |
| hsa-miR-221-3p | MIMAT0000278 | MIRT000434 | qRT-PCR//ChIP//Luciferase reporter assay//Western blot//Northern blot | Functional MTI | 20388878 |
| hsa-miR-182-5p | MIMAT0000259 | MIRT000671 | Luciferase reporter assay//Western blot | Functional MTI | 19188590 |
| hsa-miR-23a-3p | MIMAT0000078 | MIRT006284 | Immunoblot//Luciferase reporter assay//qRT-PCR | Functional MTI | 22084234 |
| hsa-miR-23a-3p | MIMAT0000078 | MIRT006284 | Immunoblot//Luciferase reporter assay//qRT-PCR | Functional MTI | 22095742 |
| hsa-miR-197-3p | MIMAT0000227 | MIRT004198 | Microarray | Functional MTI (Weak) | 16822819 |
| hsa-miR-155-5p | MIMAT0000646 | MIRT004495 | qRT-PCR//Luciferase reporter assay//Western blot | Functional MTI | 20371610 |
| hsa-miR-155-5p | MIMAT0000646 | MIRT004495 | Flow//Immunoblot//Immunofluorescence//Immunohistochemistry//Microarray//qRT-PCR//Western blot | Functional MTI | 21304824 |
| hsa-miR-155-5p | MIMAT0000646 | MIRT004495 | Proteomics | Functional MTI (Weak) | 19650740 |
| hsa-miR-96-5p | MIMAT0000095 | MIRT005450 | Luciferase reporter assay//qRT-PCR//Western blot | Functional MTI | 21203424 |
| hsa-miR-9-5p | MIMAT0000441 | MIRT007326 | Luciferase reporter assay | Functional MTI | 23509296 |
| hsa-miR-335-5p | MIMAT0000765 | MIRT017201 | Microarray | Functional MTI (Weak) | 18185580 |
| hsa-miR-744-5p | MIMAT0004945 | MIRT037525 | CLASH | Functional MTI (Weak) | 23622248 |
| hsa-miR-615-3p | MIMAT0003283 | MIRT039975 | CLASH | Functional MTI (Weak) | 23622248 |
| hsa-miR-26a-5p | MIMAT0000082 | MIRT050180 | CLASH | Functional MTI (Weak) | 23622248 |
| hsa-let-7c-5p | MIMAT0000064 | MIRT051735 | CLASH | Functional MTI (Weak) | 23622248 |
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- mirRecord
- mirRecord
MicroRNA name | mirBase ID | Target site number | MiRNA mature ID | Test method inter | MiRNA regulation site | Reporter target site | Pubmed ID |
|---|---|---|---|---|---|---|---|
| hsa-miR-155-5p | MIMAT0000646 | NA | hsa-miR-155 | {Western blot} | {overexpression by miRNA precursor transfection} | 20371610 |
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6. Text-mining results about the gene
Gene occurances in abstracts of cellular senescence-associated articles: 33 abstracts the gene occurs.
PubMed ID of the article | Sentenece the gene occurs |
|---|---|
| 27349869 | As a result, FoxO1 and FoxO3 transcription activity was recovered |
| 27237816 | Altered proliferation and altered expression of anti-aging factors, including SIRT1 and FoxO3, characterise cellular senescence |
| 27237816 | Flow cytometry and clonogenic assay were used to assess cell proliferation; western blot analysis was used for assessing nuclear expression of SIRT1 and FoxO3 |
| 27237816 | The nuclear co-localization of SIRT1 and FoxO3 was assessed by fluorescence microscopy |
| 27237816 | RESULTS: CSE decreased cell proliferation, the nuclear expression of SIRT1 and FoxO3 and increased beta galactosidase staining |
| 27237816 | CSE, reduced SIRT1 activity and FoxO3 localization on survivin promoter thus increasing survivin expression |
| 27237816 | In CSE stimulated bronchial epithelial cells carbocysteine reverted these phenomena by increasing cell proliferation, and SIRT1 and FoxO3 nuclear expression, and by reducing beta galactosidase staining and survivin expression |
| 26873092 | Foxo3 circular RNA promotes cardiac senescence by modulating multiple factors associated with stress and senescence responses |
| 26873092 | METHODS AND RESULTS: Using the approaches of molecular and cellular biology, we show that a circular RNA generated from a member of the forkhead family of transcription factors, Foxo3, namely circ-Foxo3, was highly expressed in heart samples of aged patients and mice, which was correlated with markers of cellular senescence |
| 26763397 | Our results showed that arsenic induced the nuclear translocation of FOXO1 and FOXO3a, and altered the cell cycle, with cells accumulating at the G2/M phase |
| 26469953 | The mechanism involves not only the inhibition of autophagy early induced by these stimuli in the pathway to senescence, but also the increase in levels and nuclear localization of both the cell cycle suppressors p53/p21 and the longevity promoters FOXO1A, FOXO3A and SIRT1 |
| 25945449 | RESULTS: Different transcriptional profiles were observed in young, pre-senescent and senescent HDFs, in which cellular aging increased AKT, FOXO3, CDKN1A and RSK1 mRNA expression level, but decreased ELK1, FOS and SIRT1 mRNA expression level |
| 25945449 | With tocotrienol-rich fraction treatment, gene expression of AKT, FOXO3, ERK and RSK1 mRNA was decreased in senescent cells, but not in young cells |
| 25945449 | Expression of FOXO3 and P21Cip1 proteins showed up-regulation in senescent cells but tocotrienol-rich fraction only decreased P21Cip1 protein expression in senescent cells |
| 25835220 | METHODS: We measured the expression of the deacetylase Sirtuin 1 (Sirt1) and its transcriptional target Forkhead box O3a (Foxo3a); TBARS, a well-known marker of overall oxidative stress, and catalase activity as index of antioxidation |
| 25835220 | RESULTS: Under oxidative stress induction older cells showed a progressive decrease of Sirt1 and Foxo3a expression, persistently high TBARS levels with high, but ineffective Cat activity to counteract such levels |
| 25790295 | The adaptor protein p66Shc regulates intracellular oxidant levels through the modulation of a forkhead-related transcription factor (FOXO3a) |
| 25662949 | The protein expressions for FoxO1 and FoxO3 were increased in OLETF-AL rats, but the levels of phosphorylated (p)-Akt were decreased compared to those in OLETF-CR rats |
| 25655933 | FoxO3a suppresses the senescence of cardiac microvascular endothelial cells by regulating the ROS-mediated cell cycle |
| 25655933 | FoxO3a plays an important role in the aging process and decreases with age |
| 25655933 | However, the potential regulatory roles of FoxO3a in processes involved in cardiac microvascular endothelial cell (CMEC) senescence, and its underlying molecular mechanisms have not been elucidated |
| 25655933 | This study demonstrates that FoxO3a is deactivated in senescent CMECs together with the inhibition of proliferation and tube formation |
| 25655933 | Furthermore, the activation of the antioxidant enzymes catalase and SOD, downstream FoxO3a targets, was significantly decreased, thereby leading to cell cycle arrest in G1-phase by increased ROS generation and subsequently the activation of the p27(Kip1) pathway |
| 25655933 | However, FoxO3a overexpression in primary low-passage CMECs not only significantly suppressed the senescence process by increasing the activation of catalase and SOD but also markedly inhibited ROS generation and p27(Kip1) activation, although it failed to reverse cellular senescence |
| 25655933 | Moreover, both cell viability and tube formation were greatly increased by FoxO3a overexpression in primary CMECs during continuous passage |
| 25655933 | In addition, FoxO3a, deficiency in low-passage CMECs, accelerated the senescence process |
| 25655933 | Collectively, our data suggest that FoxO3a suppresses the senescence process in CMECs by regulating the antioxidant/ROS/p27(Kip1) pathways, although it fails to reverse the cellular senescent phenotype |
| 25647160 | Treatment of keratinocytes with resveratrol transactivated FOXO3 and increased the expression of its target genes including catalase |
| 25647160 | Resveratrol's effects on both senescence and proliferation disappeared when FOXO3 was knocked down |
| 25344604 | E2F1 and FOXO3 are two transcription factors that have been shown to participate in cellular senescence |
| 25344604 | Here we use E2F1 knock-out murine Embryonic fibroblasts (MEFs), knockdown RNAi constructs, and ectopic expression of E2F1 to show that it functions by negatively regulating FOXO3 |
| 25344604 | E2F1 attenuates FOXO3-mediated expression of MnSOD and Catalase without affecting FOXO3 protein stability, subcellular localization, or phosphorylation by Akt |
| 25344604 | We mapped the interaction between E2F1 and FOXO3 to a region including the DNA binding domain of E2F1 and the C-terminal transcription-activation domain of FOXO3 |
| 25344604 | We propose that E2F1 inhibits FOXO3-dependent transcription by directly binding FOXO3 in the nucleus and preventing activation of its target genes |
| 25344604 | We conclude that there is an evolutionarily conserved signaling connection between E2F1 and FOXO3, which regulates cellular senescence and aging by regulating the activity of FOXO3 |
| 25186470 | METHODS: Small interfering RNAs (siRNAs) targeting FOXO1 (siFOXO1) and FOXO3 (siFOXO3) were transfected into human articular chondrocytes |
| 25184156 | On the contrary, sirtinol treatment causes the significantly increased level of FoxO3a, a proapoptotic transcription factor targeted by Sirt1 |
| 25166345 | We report a detailed analysis of senescence signalling via DNA damage, insulin-TOR, FoxO3a transcription factors, oxidative stress response, mitochondrial regulation and mitophagy |
| 25165029 | Molecular analysis demonstrated that deacetylation of Forkhead box O3alpha (FOXO3alpha) by SIRT1 changed the transcriptional activity of FOXO3alpha and increased resistance to the oxidative stress |
| 25077541 | We demonstrate that miR-17 targets both ADCY5 and IRS1, upregulating the downstream signals MKP7, FoxO3, LC3B, and HIF1alpha, and downregulating mTOR, c-myc, cyclin D1, and JNK |
| 25000517 | FOXO3a potentiates hTERT gene expression by activating c-MYC and extends the replicative life-span of human fibroblast |
| 25000517 | In this study, we investigate the molecular mechanisms behind SIRT1-induced potentiation of hTERT transcription and show that FOXO3a functions downstream of SIRT1 and prevents the induction of cellular senescence by enhancing hTERT gene expression |
| 25000517 | In addition, we found that FOXO3a binds to the novel binding element in the c-MYC promoter, and this interaction activates the transcription of the c-MYC gene |
| 25000517 | Taken together, this pathway might constitute the molecular basis for the anti-senescence effects of SIRT1 and FOXO3a |
| 24269635 | RESULTS: Human cartilage expressed FOXO1 and FOXO3 but not FOXO4 proteins |
| 24269635 | FOXO1 and FOXO3 were more strongly expressed the superficial and mid zone as compared to the deep zone and were mainly localized in nuclei |
| 24269635 | During human joint aging, expression of FOXO1 and FOXO3 was markedly reduced in the superficial zone of cartilage regions exposed to maximal weight bearing |
| 24269635 | In cultured chondrocytes, IL-1beta and TNF-alpha suppressed FOXO1, while TGF-beta and PDGF increased FOXO1 and FOXO3 expression |
| 24269635 | FOXO1 and FOXO3 phosphorylation was increased by IL-1beta, PDGF, bFGF, IGF-1, and the oxidant t-BHP |
| 23542362 | Furthermore, oxidant/carbonyl stress-mediated reduction of SIRT1 leads to the loss of its control on acetylation of target proteins including p53, RelA/p65, and FOXO3, thereby enhancing the inflammatory, prosenescent, and apoptotic responses, as well as endothelial dysfunction |
| 23542362 | In this review, the mechanisms of cigarette smoke/oxidant-mediated redox posttranslational modifications of SIRT1 and its roles in PARP1 and NF-kappaB activation, and FOXO3 and eNOS regulation, as well as chromatin remodeling/histone modifications during inflammaging, are discussed |
| 23525956 | Using human umbilical endothelial cells (HUVECs), we show that syringaresinol treatment induced binding of FOXO3 to the SIRT1 promoter in a sequence-specific manner, leading to induction of SIRT1 expression |
| 23525956 | Increased SIRT1 expression in HUVECs by syringaresinol treatment delayed cellular senescence and improved various markers of endothelial functions in a FOXO3 dependent manner |
| 22546858 | These effects were due to the ability of SIRT1 to deacetylate the FOXO3 transcription factor, since Foxo3 deficiency diminished the protective effect of SRT1720 on cellular senescence and emphysematous changes |
| 22489168 | These findings suggest a novel mechanism by which FoxO3A factors can activate autophagy via metabolic alteration |
| 21707762 | Previous studies showed that beta-catenin can regulate FoxO3a and this association was enhanced in cells exposed to oxidative stress |
| 21418510 | Data also implied that this effect was associated with altered actions of FoxO3 and GSK-3beta |
| 20716932 | Aging-regulating genes p66shc, Sirtuin, FOXO3a and Klotho are new important factors which are stimulated by ROS signaling |
| 20656682 | Vitamin D3 up-regulated protein 1(VDUP1) is regulated by FOXO3A and miR-17-5p at the transcriptional and post-transcriptional levels, respectively, in senescent fibroblasts |
| 20656682 | Subsequently, we found that FOXO3A, whose activity increased in senescent cells, transcriptionally up-regulates VDUP1 expression and miR-17-5p, whose expression decreased in senescent cells, directly interacted with the 3'-untranslated region of VDUP1 transcripts, and destabilized VDUP1 mRNA in young cells |
| 20656682 | These results indicated that VDUP1 expression was regulated by FOXO3A at the transcriptional level and by miR-17-5p at the post-transcriptional levels during the senescence process |
| 20528770 | In contrast, up-regulation of Nuak2 (NUAK family, SNF1-like kinase 2) and down-regulation of Lonp2 (Lon peptidase 2), Foxo3a (forkhead box O3a), Sod1 (copper/zinc superoxide dismutase) and Sesn1 (sestrin 1) in the kidneys of recuperated offspring suggest that protein homoeostasis and resistance to oxidative stress are compromised, leading to accelerated cellular senescence in these shorter-lived mice |
| 17635417 | The FOXO3a (forkhead box O3a) protein level was increased in old IGFBP3 shRNA cells |
| 17635417 | The treatment of young HUVECs with IGFBP3 repressed the levels of FOXO3a protein |
| 15741276 | Down-regulation of a forkhead transcription factor, FOXO3a, accelerates cellular senescence in human dermal fibroblasts |
| 15741276 | The FOXO family of forkhead transcription factors, FOXO1, FOXO3a, and FOXO4, play a critical role in this signal transduction pathway |
| 15741276 | However, the impact of FOXO3a activation on life span of primary cultured human dermal fibroblasts (HDFs) is unknown |
| 15741276 | To investigate the role of FOXO3a in the regulation of cellular senescence, we prepared FOXO3a-siRNA stable HDFs |
| 15741276 | We found that the down-regulation of FOXO3a RNA and protein in HDFs induced many senescent phenotypes, including changes in cell morphology, increases in population doubling times, senescence-associated beta-galactosidase staining and the cellular reactive oxygen species, and up-regulation of p53/p21 protein expression |
| 15741276 | Our data provide evidence of the key role of FOXO3a transcription factor as a mediator of cellular senescence in HDFs, and suggest that the mechanism of senescence is conserved in HDFs |
| 14713953 | Constitutive activation of Akt promotes senescence-like arrest of cell growth via a p53/p21-dependent pathway, and inhibition of forkhead transcription factor FOXO3a by Akt is essential for this growth arrest to occur |
| 12470826 | We have previously demonstrated that collagenase expression is under positive regulation by the transcription factor FKHRL1 and that this transcription factor is under negative regulation by the phosphatidylinositol 3-kinase(PI3K)/Akt(PKB) pathway |
| 11751876 | Our results indicate that Akt-mediated signals, acting through the forkhead transcription factor FKHRL1, can regulate collagenase expression in WI-38 fibroblasts |
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